Cystinuria is a disease caused by congential metabolic disorders wherein the reabsorbing function of cystine, lysine, ornithine and arginine into renal tubules is hereditarily damaged and an excessive amount of amino acids are excreted into urine. Amino acids except cystine are soluble in urine and do not cause a problem. Cystine, however, is very slightly soluble in urine and crystallizes to form stones in the urinary tract. The main direct complaints of cystinuria patients are colic, hematuria, etc. caused by cystine stones. Sometimes pyelonephritis or cystitis is caused by a secondary infection.
Therapeutic methods can be classified into two surgical methods, namely an operative removal of cystine stones and a destruction of cystine stones by a shock wave, and a dissolution of cystine stones. For dissolution, a fluid intake method, an alkalization method and a medicinal method with D-penicillamine or tiopronin are known (Urol. Clin. North. Am., 14, 339 (1987)).
If a cystine stone is removed by the surgical operation, the cystinuria patients can be released from the direct complaints. However the latter methods, namely the dissolution, still contain a problem of recurrence of cystine stone formation. Furthermore, there exist problems in the surgical methods. For example, the stone sometimes exists at a difficult place to be removed by an operation, and the cystine stone can be hardly destructed by the shock wave because the stone is harder than other kinds of stones. Therefore, the latter method, which can dissolve the cystine stone and prevent a recurrence of the stone formation, is very important for treatment of cystinuria.
However, the fluid intake method and alkalization method have some disadvantages. For example, in the fluid intake method, it is necessary for an adult patient to drink 4-6 liters of water a day and such large water intake is very hard to a patient. In the alkalization method, pH of the urine is raised to dissolve the cystine stones by administration of alkali such as sodium hydrogen carbonate, while it gives good conditions to form phosphate stones.
Therefore, it was devised to convert cystine into a water soluble mixed disulfide by administration of a medical substance having a sulfhydryl group to dissolve the cystine stone and further to prevent a recurrence of the stone formation. D-penicillamine, a medical substance applied first, was effective, but had a disadvantage of serious side effects. It was reported that the use of tiopronin, .alpha.-mercaptopropionylglycine, instead of D-penicillamine can reduce the side effects (Proc. Soc. Exptl. Biol. & Med., 129, 927 (1968), Urol. Clin. North. Am., 14, 339 (1987)). However, more effective and safer medical substances are desired for treatment of cystinuria.
Bucillamine, a main ingredient of this invention, has been known as a safe medical substance and to be useful as an anti-rheumatic, a liquefactant of sputum, a suppressant of liver disorders or an anti-cataract agent (Japanese Patent Publications 11888/1985, 5388/1981, 13922/1987 and 13964/1988). It is known that bucillamine is useful in various therapeutic fields, but an application to cystinuria has never been studied.